Chronic hepatitis B and occult infection in chemotherapy patients - evaluation in oncology and hemato-oncology settings: The CHOICE study.

BACKGROUND: Reactivation of hepatitis B virus (HBV) infection is a well-known risk that can occur spontaneously or following immunosuppressive therapies, including cancer chemotherapy. HBV reactivation can cause significant morbidity and even mortality, which are preventable if at-risk individuals are identified through screening and started on antiviral prophylaxis. AIM: To determine the prevalence of chronic HBV (CHB) and occult HBV infection (OBI) among oncology and hematology-oncology patients undergoing chemotherapy. METHODS: In this observational study, the prevalence of CHB and OBI was assessed among patients receiving chemotherapy. Serological markers of HBV infection [hepatitis B surface antigen (HBsAg)/anti-hepatitis B core antigen (HBc)] were evaluated for all patients. HBV DNA levels were assessed in those who tested negative for HBsAg but positive for total anti-HBc. RESULTS: The prevalence of CHB in the study cohort was determined to be 2.3% [95% confidence interval (95%CI): 1.0-4.2]. Additionally, the prevalence of OBI among the study participants was found to be 0.8% (95%CI: 0.2-2.3). CONCLUSION: The findings of this study highlight the importance of screening for hepatitis B infection in oncology and hematology-oncology patients undergoing chemotherapy. Identifying individuals with CHB and OBI is crucial for implementing appropriate antiviral prophylaxis to prevent the reactivation of HBV infection, which can lead to increased morbidity and mortality.

Unknown presentation of a rare genetic disorder: Monogenic diabetes in young type 4 presenting with hepatic cysts and procoagulant state.

Maturity onset diabetes in young (MODY) is the most common form of monogenic diabetes, which characteristically presents in adolescents and young adults. Till date, pathogenic variations involving 14 different genes have been causally implicated with the development of MODY. Maturity onset diabetes in young type 4 (MODY-4) is a very rare form of MODY. We present here case of 28-year-old nonobese male patient with distinct family history of diabetes spanning two generations, incidentally, detected to have a rare form of diabetes on genetic analysis when he presented with recurrent thromboembolic manifestations: deep vein thrombosis and pulmonary thromboembolism. Our case highlights a previously unknown disease association of a rare genetic disorder. Increasing awareness about this genetic disorder and early identification of such cases will enhance our understanding of hitherto unknown disease associations and the pathophysiological role of genetic mutations. This may contribute to the improved treatment and prevention of debilitating diseases such as diabetes.

Diabetes mellitus as a consequence of acute severe pancreatitis: Unraveling the mystery.

The occurrence of diabetes mellitus (DM) in pancreatitis is being increasingly recognized lately. Diabetes can develop not only with chronic pancreatitis but even after the first episode of acute pancreatitis (AP). The incidence of diabetes after AP varies from 18% to 23% in 3 years and reaches up to 40% over 5 years. The exact pathogenesis of diabetes after AP is poorly understood and various mechanisms proposed include loss of islet cell mass, AP-induced autoimmunity, and alterations in the insulin incretin axis. Risk factors associated with increased risk of diabetes includes male sex, recurrent attacks of pancreatitis, presence of pancreatic exocrine insufficiency and level of pancreatitic necrosis. Diagnosis of post-pancreatitis DM (PPDM) is often excluded. Treatment includes a trial of oral antidiabetic drugs in mild diabetes. Often, insulin is required in uncontrolled diabetes. Given the lack of awareness of this metabolic disorder after AP, this review will evaluate current information on epidemiology, risk factors, diagnosis and management of PPDM and identify the knowledge gaps.

Coexistence of human immunodeficiency virus infection and autoimmune hepatitis: A double trouble.

A wide spectrum of hepatobiliary manifestations occur in Human Immunodeficiency Virus (HIV)-infected patients. Among the common causes are the infectious hepatitis, drug-related hepatitis, opportunistic infections, non-alcoholic steatohepatitis, HIV cholangiopathy and neoplasm. Auto-immune hepatitis (AIH) is rarely reported in this setting. We present two different presentations of auto immune hepatitis in HIV positive patients. One developed jaundice and ascites as a consequence of liver decompensation and other exhibited cholestatic pattern. Their serology and liver biopsy confirmed autoimmune hepatitis as underlying aetiology. We would like to share the clinical improvement with simultaneous immunosuppressive therapy and combination Anti Retroviral Therapy (cART). There are no documented cases on this issue from the Indian subcontinent that we are aware of.

Real-world experience of monoclonal antibodies in mild-to-moderate COVID-19 patients at a tertiary care center.

Background: Neutralizing antibodies cocktail (casirivimab and imdevimab) has received emergency use authorization recommendation by Food and Drug Administration (FDA) and WHO for mild-to-moderate COVID-19 infection in specific high-risk groups. Antibodies cocktail has shown promising results in preventing progression to severe disease, but the real-world experience is still evolving. Herein, we present a retrospective analysis of 22 patients who were administered the antibodies cocktail between August 2021 and March 2022 at our tertiary care center. Methods: We conducted an observational retrospective analysis of clinicoradiological, inflammatory parameters, progression of the disease, and outcome among 22 mild and moderate COVID-19 patients treated with antibodies cocktail. Results: The mean age was 67.7 years (SD ± 18.3) and comprised of 13 males (59%), while 9 were females (40.9%). Nine (40.9%) patients were fully vaccinated with two doses, nine (40.9%) were partially vaccinated with one dose while four patients (18.2%) were unvaccinated, and the rest were unvaccinated. Diabetes and hypertension were the commonest comorbidities; hematological and solid organ malignancies were other comorbidities. Eight patients had radiological opacities consistent with COVID-19 pneumonia and had shown significant regression in four patients after the therapy. None of our patients required supplemental oxygen or progressed to severe acute respiratory distress syndrome. All patients were discharged in a stable condition within 6 days of the therapy. Conclusions: The neutralizing antibodies cocktail has shown encouraging results in our analysis in preventing progression to severe disease in patients with high-risk conditions.

Controversies in the management of acute pancreatitis: An update.

This review summarized the current controversies in the management of acute pancreatitis (AP). The controversies in management range from issues involving fluid resuscitation, nutrition, the role of antibiotics and antifungals, which analgesic to use, role of anticoagulation and intervention for complications in AP. The interventions vary from percutaneous drainage, endoscopy or surgery. Active research and emerging data are helping to formulate better guidelines. The available evidence favors crystalloids, although the choice and type of fluid resuscitation is an area of dynamic research. The nutrition aspect does not have controversy as of now as early enteral feeding is preferred most often than not. The empirical use of antibiotics and antifungals are gray zones, and more data is needed for conclusive guidelines. The choice of analgesic is being studied, and the recommendations are still evolving. The position of using anticoagulation is still awaiting consensus. The role of intervention is well established, although the modality is constantly changing and favoring endoscopy or percutaneous drainage rather than surgery. It is evident that more multicenter randomized controlled trials are required for establishing the standard of care in these crucial management issues of AP to improve the morbidity and mortality worldwide.

The prevalence of osteoporosis and its association with serum testosterone and serum vitamin D in the elderly male population: A cross-sectional study.

Background: Male osteoporosis is under-diagnosed and poorly studied. With the ageing population, osteoporotic fracture in men is an emerging health problem. The aim of this study was to study the prevalence of osteoporosis and its association with serum testosterone and serum vitamin D in elderly men (>60 years old) attending the outpatient department (OPD). Methods: An observational cross-sectional study was performed in elderly men (>60 years old) attending OPD of a tertiary care hospital of Western Maharashtra between April 2017 and June 2019. Patients with rheumatological disorders, history of vertebral/femoral fractures, chronic kidney disease, chronic liver disease, thyroid disorders and alcohol dependence were excluded. Data were analysed using the chi-square test and descriptive statistics. Results: In total, 408 male patients were included. The mean age was 68.33 years. Osteoporosis was seen in 39.5% of patients (161/408) with a T score of ≤2.5. Osteopenia was noted in 48.3% of patients (197/408). T and Z scores had significant correlation (p = <0.001). Only 12% of elderly men had normal bone mineral density score. Serum testosterone, chronic obstructive pulmonary disease (COPD) and benign prostatic hypertrophy (BPH) were significantly associated with male osteoporosis with a p-value of 0.019, 0.016 and 0.010, respectively. Vitamin D levels, type 2 diabetes mellitus, hypertension and coronary artery disease did not show any significant association with male osteoporosis. Conclusion: Osteoporosis was noted in 39.5% of the elderly men. In addition, decreased testosterone, COPD and BPH were significantly associated with male osteoporosis. It is important to screen elderly men to diagnose osteoporosis early and prevent osteoporotic fractures.

Anemia in cirrhosis: An underestimated entity.

Anemia in a patient with cirrhosis is a clinically pertinent but often overlooked clinical entity. Relevant guidelines highlight the algorithmic approach of managing a patient of cirrhosis presenting with acute variceal hemorrhage but day-to-day management in hospital and out-patient raises multiple dilemmas: Whether anemia is a disease complication or a part of the disease spectrum? Should iron, folic acid, and vitamin B complex supplementation and nutritional advice, suffice in those who can perform tasks of daily living but have persistently low hemoglobin. How does one investigate and manage anemia due to multifactorial etiologies in the same patient: Acute or chronic blood loss because of portal hypertension and bone marrow aplasia secondary to hepatitis B or C viremia? To add to the clinician's woes the prevalence of anemia increases with increasing disease severity. We thus aim to critically analyze the various pathophysiological mechanisms complicating anemia in a patient with cirrhosis with an emphasis on the diagnostic flowchart in such patients and proposed management protocols thereafter.

Association of promoter methylation status of NRF2 and PNPLA3 genes in alcoholic liver disease.

BACKGROUND: Alcoholic liver disease (ALD) is the leading cause of chronic liver disease. In the liver, metabolism of alcohol occurs through multiple mechanisms and it results in the generation of various toxic products. Multiple genetic causes have been identified that are associated with the development and progression of ALD. The present study assessed the promoter site methylation status of nuclear factor erythroid 2-related factor 2 (NRF2) and patatin-like phospholipase domain-containing protein-3 (PNPLA3) genes in different subgroups of ALD. METHODS: The patients recruited were cases of alcohol dependence syndrome with hepatic dysfunction, compensated cirrhosis, decompensated cirrhosis, and acute-on-chronic liver failure due to alcohol as an etiology along with healthy control subjects. Routine biochemical investigations were performed along with methylation-specific polymerase chain reaction (MS-PCR) to qualitatively assess the promoter methylation status of NRF2 and PNPLA3 in all these cases. RESULTS: There was significant difference in methylation status of NRF2 gene in ALD when compared to healthy controls but there was no such difference in PNPLA3. All biochemical and clinical parameters studied were significantly different in subgroups of ALD except the serum aspartate aminotransferase (AST) level. Subgroups of ALD did not show any significant association with NRF2 or PNPLA3 methylation status. Gamma-glutamyl transferase (GGT) and creatinine levels in serum were significantly associated with the methylation status of NRF2 gene while no such association was seen with PNPLA3 gene. Model for end-stage liver disease (MELD) score varied differentially with NRF2 methylation and PNPLA3 methylation but there was no statistical significance. CONCLUSIONS: The present study showed that methylation status of NRF2 and PNPLA3 genes could not differentiate between subgroups of alcoholic liver diseases. However, the unmethylation of NRF2 promoter is associated with higher serum levels of GGT.

Current and emerging therapeutic strategies in pancreatic cancer: Challenges and opportunities.

Pancreatic carcinoma (PC) is one of the leading causes of cancer-related deaths worldwide. Despite early detection and advances in therapeutics, the prognosis remains dismal. The outcome and therapeutic approach are dependent on the stage of PC at the time of diagnosis. The standard of care is surgery, followed by adjuvant chemotherapy. The advent of newer drugs has changed the landscape of adjuvant therapy. Moreover, recent trials have highlighted the role of neoadjuvant therapy and chemoradiotherapy for resectable and borderline resectable PC. As we progress towards a better understanding of tumor biology, genetics, and microenvironment, novel therapeutic strategies and targeted agents are now on the horizon. We have described the current and emerging therapeutic strategies in PC.

Rodenticide-induced acute liver failure - Uncommon presentation of commonly available poison.

Rodenticide or 'rat poison' is easily available in a predominantly agrarian economy such as India. Metal phosphides or yellow phosphorous are two common rodenticides. Acute liver failure caused by accidental or suicidal poisoning with rodenticides has been infrequently reported in literature. Liver transplantation offers the best chances of survival in severe intoxication. However, the availability of liver transplantation in resource-limited settings presents a challenge. N-acetyl cysteine has been successfully used in paracetamol poisoning. Its use in rodenticide-induced acute liver failure is not so well known. We report three cases of rodenticide-related acute liver failure, one of them being a pregnant lady. All three patients were given N-acetyl cysteine and two patients improved. It is possible that the administration of N-acetyl cysteine contributed to the improvement in these two.

Hepatitis B vaccination in Indian children: Seroprotection and age-related change in antibody titres.

BACKGROUND: Childhood immunization against hepatitis B is one of the most effective strategies for reducing the global burden of chronic hepatitis B infection and its sequelae. There are limited data from India on both the anti-Hep B antibody titres in children after vaccination and the age-related decline in the titres. This study was planned to estimate the proportion of children in the age group of 1-10 years who develop protective levels of anti-hepatitis B antibodies after childhood vaccination and to examine the change in antibody titres with age in these children. METHODS: A hospital-based cross-sectional study was carried out in children admitted to the hospital for various ailments. Basic demographic data, vaccination history and HBsAg status of the mother were recorded. All the enrolled children were evaluated for HBsAg and anti hepatitis B surface antibody (anti-HBS) titres. Institutional ethical clearance was obtained, and informed consent from the parents of the children was taken before drawing samples. RESULTS: We found that 68.86% Confidence Interval ((CI): 59.8-76.8%) of the children showed protective antibody titres after vaccination, while 31.14% (CI: 23.1-40.2%) of the children had titres less than 10 IU/L. Although 100% of children in the age group from birth to three years had titres more than 10 IU/L, this percentage showed a decline across the age groups, and 60% of children aged 9-10 years had titres less than 10 IU/L. CONCLUSION: Childhood vaccination against hepatitis B is effective in 68% children, and the antibody levels showed a steady decline with increasing age.

Profile of Hepatobiliary Dysfunction in Hematopoietic Stem Cell Transplant Recipients - An Indian Perspective.

BACKGROUND/AIMS: Hematopoietic stem cell transplantation (HSCT) is an established curative modality for various hematological malignancies and other diseases. Hepatobiliary dysfunction and subsequent sequelae constitute a common cause of morbidity and mortality in post-transplant scenario. However, data among Indian HSCT recipients is lacking. METHODS: One hundred and one HSCT recipients (37 prospective and 64 retrospective) were followed up for hepatobiliary dysfunction in the post-transplant period. The causes for hepatobiliary dysfunction were categorized as sinusoidal obstruction syndrome (SOS), formerly known as veno-occlusive disease (VOD); acute and chronic graft-versus- host disease (GVHD); drug-induced liver injury (DILI); viral infections and miscellaneous causes including bacterial, fungal and unknown causes based on clinical and laboratory evidence. RESULTS: Among the 101 transplants, 56.44% (n = 57) were allogenic transplants, and 43.56% (n = 44) were autologous transplants. Hepatobiliary dysfunction was observed among 71 (70.30%) patients in first 30 days and overall, among 78 (77.23%) patients. Incidence of hepatobiliary dysfunction was higher among allogenic transplant patients compared to autologous transplants (91.23% vs. 59.09%, p < 0.001). The most common cause of hepatobiliary dysfunction reported was Drug-induced liver injury (DILI). In most cases, however, hepatobiliary dysfunction was multifactorial. Sinusoidal obstruction syndrome (15.79%), acute liver GVHD (31.58%), chronic liver GVHD (33.33%) and viral infection/reactivation (26.32%) were reported only in allogenic transplant patients. 15 (14.85%) patients died of which 14 patients had hepatobiliary dysfunction, commonest cause being infections. CONCLUSION: Our study reported a higher incidence of hepatobiliary dysfunction among Indian population post HSCT and was associated with significant mortality. In majority of the cases, the cause is multifactorial and pose a diagnostic dilemma and challenges in therapy.

Olfactory Dysfunction Among Asymptomatic Patients with SARS CoV2 Infection: A Case-Control Study.

Olfactory dysfunction (hyposmia, anosmia) is a well-recognized symptom in patients with coronavirus disease-19 (COVID-19). Studies of olfactory dysfunction in asymptomatic patients have not been reported. We conducted a study looking for the presence of olfactory dysfunction with an objective assessment tool in asymptomatic Covid 19 and compared it with patients with mild COVID-19 and age-matched controls. We recruited 57 male patients each of Mild COVID-19, asymptomatic Covid 19, and healthy controls for the study. All participants underwent evaluation of smell threshold by Butanol Threshold test (BTT) and ability to distinguish common odors by Smell identification test. The scores of each test were recorded on a numerical scale. The participants in all three arms were matched for age, history of smoking, and pre-existing medical conditions. The mean scores of the Butanol Threshold test in Mild COVID-19, asymptomatic Covid 19 and controls were 2.95 ± 2.25 (0-7.5), 3.42 ± 2.23 (0-7.5), and 4.82 ± 1.86 (0-8), respectively. A one-way ANOVA showed a significant difference between groups (df 2, MS 53.78, F 11.94, p < 0.005). Intergroup differences using the student T-test showed significantly low BTT scores in Mild COVID-19 (p < 0.005) and asymptomatic (p < 0.005) as compared to control. BTT scores could not distinguish between asymptomatic patients and control. The smell threshold was impaired in asymptomatic Covid 19 and Mild COVID-19. Butanol Threshold Test score could not differentiate between asymptomatic Covid 19 and controls.

Microbiology of bile in extrahepatic biliary obstruction: A tropical experience.

PURPOSE: Bile is considered sterile, but in obstructed biliary system, growth of micro-organisms results in bacteraemia and toxaemia. We analysed bacterial profile of patients undergoing endoscopic retrograde cholangiopancreatography (ERCP) and evaluated antibiotic resistance patterns to formulate strategy for antibiotics in patients undergoing ERCP. MATERIALS AND METHODS: Patients with cholestasis who underwent ERCP were enrolled. Bile, collected aseptically, was cultured. Positive cultures were processed for isolate identification and antibiotic susceptibility. RESULTS: One hundred and sixty-three patients (78 females; mean age - 55.1 ±â€¯15.8 years) were enrolled and divided into two groups: Group I (n = 99) were naïve and Group II (n = 64) had undergone ERCP and stenting previously. Positive culture was seen in 68.1% (n = 111) with monomicrobial growth in 74.8% (n = 83) and poly-microbial growth in 25.2% (n = 28). Culture positivity was common in Group II vis-a-vis Group I (84.4% vs. 57.5%). Poly-microbial growth was significantly more common in Group II (35.2% vs. 15.8%, P = 0.028). Gram-negative bacilli were the predominant organisms isolated with Escherichia coli, Pseudomonas aeruginosa and Klebsiella pneumoniae comprising 70% of the isolates. The most sensitive antibiotics were piperacillin-tazobactam and imipenem. The sensitivity of vancomycin, against Enterococcus spp. was in the range of 60%-70%. CONCLUSION: Cholestasis leads to bacterial colonisation in most cases, regardless of the presence of a biliary stent. Biliary stent however predisposes to a polymicrobial growth. Most of the commonly used antibiotics continue to have significant sensitivity and may be used empirically. However, previously stented patients may have a higher incidence of infection with Enterococcus spp. and may require specific therapy.

Epidemiology of hepatitis C virus infection in a tertiary care hospital.

BACKGROUND: There are epidemiological lacunae in literature of hepatitis C virus (HCV) infection. We report a prospective observational study of asymptomatic HCV infected patients from a tertiary care Government Hospital. METHODS: All consecutive asymptomatic antibodies to hepatitis C virus (anti-HCV) positive patients were studied from July 2011 to April 2016. Patients were reviewed for demographic factors including symptom profile, risk factors, family screening, and point prevalence in relation to various districts of Punjab and Haryana. RESULTS: One thousand twelve patients were studied with median age of 52 years (range:13-85) with a male to female ratio of 0.87. Eight hundred (79.25%) patients were from Punjab and 110 (10.67%) from Haryana. Forty percent patients were in 40-60 age group. Six hundred seventy patients (66.21%) did not have any apparent risk factor, 274 (27.08%) had one risk factor, and 68 patients (6.72%) had > 2 risk factors. Commonest risk factor was h/o surgery in 243 patients (24.01%), 32 patients had h/o IV drug abuse and 29 among them were < 30 years. Three hundred and sixty-seven families and children were screened, and 27 spouses and 16 children were found to be anti-HCV positive. The risk factor of IV drug abuse was more common in the younger adults with age ≤ 30 years as compared with age > 30 years (p = 0.001). CONCLUSION: HCV infection was common in certain districts of Punjab and common in adults of 40-60 years. This finding needs to be confirmed in larger population-based study. The IV drug abuse is the risk factor of concern among young adults.

Association of liver cirrhosis severity with anemia: does it matter?

BACKGROUND: The etiology of anemia in liver disease is diverse and often multifactorial. Anemia is more severe in advanced stages of liver cirrhosis and can be a predictor of the severity of liver disease. METHODS: In this cross-sectional observational study, we included 181 cirrhotic patients with anemia owing to liver cirrhosis and its complications. The population was divided into 2 groups based on the model for end-stage liver disease (MELD) score and the severity of anemia was assessed in the 2 groups. Similarly, hemoglobin levels were assessed in 3 groups based on the Child-Turcotte-Pugh (CTP) classification. RESULTS: There was a statistically significant correlation between CTP class and hemoglobin (P<0.001), with the lowest hemoglobin levels in CTP C patients. The correlation coefficient between hemoglobin and MELD score was -0.671 and was statistically significant, establishing that hemoglobin levels decrease with increasing severity of liver cirrhosis. Of 58 patients with macrocytosis, 45 (77.6%) had a MELD score of >12, whereas only 13 patients (22.4%) had a MELD score of <12. This difference was statistically significant (P<0.0001). CONCLUSIONS: This study shows that hemoglobin levels decrease with increasing severity of liver disease; thus, this measure can be used in the initial assessment of patients to give a picture of the severity of the disease. A larger prospective trial is needed to establish the use of hemoglobin levels for assessing severity and predicting mortality in patients with liver cirrhosis.